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Sensory ataxic neuropathy in golden retriever dogs is caused by a deletion in the mitochondrial tRNATyr gene
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
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2009 (English)In: PLoS Genetics, ISSN 1553-7390, Vol. 5, no 5, e1000499- p.Article in journal (Refereed) Published
Abstract [en]

Sensory ataxic neuropathy (SAN) is a recently identified neurological disorder in golden retrievers. Pedigree analysis revealed that all affected dogs belong to one maternal lineage, and a statistical analysis showed that the disorder has a mitochondrial origin. A one base pair deletion in the mitochondrial tRNA(Tyr) gene was identified at position 5304 in affected dogs after re-sequencing the complete mitochondrial genome of seven individuals. The deletion was not found among dogs representing 18 different breeds or in six wolves, ruling out this as a common polymorphism. The mutation could be traced back to a common ancestor of all affected dogs that lived in the 1970s. We used a quantitative oligonucleotide ligation assay to establish the degree of heteroplasmy in blood and tissue samples from affected dogs and controls. Affected dogs and their first to fourth degree relatives had 0-11% wild-type (wt) sequence, while more distant relatives ranged between 5% and 60% wt sequence and all unrelated golden retrievers had 100% wt sequence. Northern blot analysis showed that tRNA(Tyr) had a 10-fold lower steady-state level in affected dogs compared with controls. Four out of five affected dogs showed decreases in mitochondrial ATP production rates and respiratory chain enzyme activities together with morphological alterations in muscle tissue, resembling the changes reported in human mitochondrial pathology. Altogether, these results provide conclusive evidence that the deletion in the mitochondrial tRNA(Tyr) gene is the causative mutation for SAN.

Place, publisher, year, edition, pages
2009. Vol. 5, no 5, e1000499- p.
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-119519DOI: 10.1371/journal.pgen.1000499ISI: 000267083000007PubMedID: 19492087OAI: oai:DiVA.org:uu-119519DiVA: diva2:300362
Available from: 2010-02-26 Created: 2010-02-26 Last updated: 2014-05-28Bibliographically approved

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Holmqvist, ErikHeidrich, NadjaWagner, Gerhart E. H.Andersson, Leif
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Department of Medical Biochemistry and MicrobiologyDepartment of Cell and Molecular Biology
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